Hirano M
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1994 May;69(3):453-65.
In this study reconstitution of lymphoid tissues under the influence of subclinical graft versus host reaction (GVHR) was investigated. Lethally irradiated recipient mice (AKR: H-2k, Mls-1a) were reconstituted with donor (B10: H-2b, Mls-1b) bone marrow (BM) cells treated with anti-Thy 1 antibody alone without complement (GVHR chimeras). When their immunological reconstitution was analysed and compared with that of AKR recipients which had been reconstituted with B10 BM treated with anti-Thy 1 and complement (Control chimera), both of these chimeras all survived more than 100 days without showing clinical signs of GVHD. Full donor chimerism was accomplished at an early stage after BM transplantation (BMT) in GVHR chimeras, whereas substantial number of recipient T cells persisted in Control chimeras during the entire observation period. No significant difference was observed in the reconstitution of the thymus and spleen between the Control and GVHR chimeras. By contrast, the reconstitution of lymph nodes (LN) in GVHR chimeras was inhibited. The apparent failure of LN reconstitution was attributed to damage of LN structure involved in homing of lymphocytes, but not attributable to damage of lymphocytes themselves. Since donor CD8+ T cells caused the damage, target antigens of this damage appeared to be H-2 class I molecules in the present system. Furthermore, clonal deletion of V beta 6+T cells that are reactive to recipient Mls-1a antigen was induced in Control chimeras but abrogated in the GVHR chimeras. The latter abrogation of clonal deletion of V beta 6+T cells appeared to result from the early disappearance of recipient T cells in these GVHR chimeras.
在本研究中,对亚临床移植物抗宿主反应(GVHR)影响下淋巴组织的重建进行了研究。用仅抗Thy 1抗体处理而无补体的供体(B10:H-2b,Mls-1b)骨髓(BM)细胞重建经致死剂量照射的受体小鼠(AKR:H-2k,Mls-1a)(GVHR嵌合体)。当分析其免疫重建并与用抗Thy 1和补体处理的B10 BM重建的AKR受体(对照嵌合体)的免疫重建进行比较时,这两种嵌合体均存活超过100天,未显示出移植物抗宿主病(GVHD)的临床症状。在GVHR嵌合体中,骨髓移植(BMT)后早期实现了完全供体嵌合,而在整个观察期内,对照嵌合体中仍有大量受体T细胞持续存在。对照嵌合体和GVHR嵌合体之间胸腺和脾脏的重建未观察到显著差异。相比之下,GVHR嵌合体中淋巴结(LN)的重建受到抑制。LN重建的明显失败归因于参与淋巴细胞归巢的LN结构的损伤,而不是淋巴细胞自身的损伤。由于供体CD8 + T细胞造成了这种损伤,在本系统中,这种损伤的靶抗原似乎是H-2 I类分子。此外,对照嵌合体中诱导了对受体Mls-1a抗原反应的Vβ6 + T细胞的克隆缺失,但在GVHR嵌合体中被消除。GVHR嵌合体中Vβ6 + T细胞克隆缺失的后者消除似乎是由于这些GVHR嵌合体中受体T细胞的早期消失所致。